Methods for treating cancer by enhancing intratumoral immune response

Abstract

Provided herein are methods that can be used to produce a local immune response in cancer tissue and/or enhance effectiveness of cancer treatment in a subject through application of one or more combinations of: an ablative fractional laser procedure, a checkpoint inhibitor, and an endosomal TLR agonist (e.g., a TLR3, TLR7, TLR8 or TLR9 agonist).

1 . A method for treating cancer in a subject, the method comprising:
 (a) administering at least one drug to a subject having a tumor, and   (b) contacting tissue of the tumor with a fractional laser,   thereby treating cancer in the subject.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the at least one drug is an immune checkpoint inhibitor. 
     
     
         4 . The method of  claim 3 , wherein the immune checkpoint inhibitor is an inhibitor of PD1, PDL1, TIM-3, or CTLA4. 
     
     
         5 . The method of  claim 3 , wherein the immune checkpoint inhibitor is ipilimumab, tremelimumab, nivolumab, or pembrolizumab. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the at least one drug is an agonist of TLR3, TLR7, TLR8 or TLR9. 
     
     
         9 . The method of  claim 8 , wherein the TLR7 agonist is imiquimod, reiquimod, or gardiquimod. 
     
     
         10 .- 15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein the cancer is melanoma or pancreatic cancer. 
     
     
         17 . The method of  claim 1 , wherein the fractional laser is a CO2 laser. 
     
     
         18 . The method of  claim 1 , wherein the fractional laser penetrates to a depth of at least 0.1 mm into the tumor tissue. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein treatment with the fractional laser does not damage the stratum corneum. 
     
     
         21 . The method of  claim 1 , wherein treatment with the fractional laser does not induce scarring or crusting of the tumor tissue. 
     
     
         22 . The method of  claim 1 , wherein the area of treatment comprises at least 0.25 mm 2 . 
     
     
         23 . The method of  claim 1 , wherein the energy of the fractional laser is 1 mJ to 200 mJ. 
     
     
         24 . The method of  claim 23 , wherein 50 mJ of energy is used for a superficial lesion and 200 mJ of energy is used for a deep tumor. 
     
     
         25 . The method of  claim 1 , wherein the pulse duration of the fractional laser is 100 usec to 10 msec. 
     
     
         26 . The method of  claim 25 , wherein the pulse duration of the fractional laser is 2 msec. 
     
     
         27 . The method of  claim 1 , wherein the spot size of the fractional laser is 10 um to 1 mm. 
     
     
         28 . The method of  claim 1 , wherein the penetration depth of the fractional laser is ⅓ the depth of the tumor. 
     
     
         29 .- 57 . (canceled) 
     
     
         58 . A method for treating cancer in a subject, the method comprising:
 (a) administering at least one drug to a subject having a tumor, and   (b) contacting tissue of the tumor with radiofrequency (RF) energy, thereby treating cancer in the subject.   
     
     
         59 . A method for treating cancer in a subject, the method comprising:
 (a) administering at least one drug to a subject having a tumor, and   (b) contacting tissue of the tumor to form microscopic treatment zones (MTZs), thereby treating cancer in the subject.